Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

cancer > cell cycle 6: apoptosis > Flashcards

cell cycle 6: apoptosis Flashcards

1
Q

why do you need programmed cell death?

A

to kill:

  • harmful cells (eg cells with viral infection / dna damage)
  • developmentally defective cells (eg b lymphocytes with self antibodies)
  • excess / unneccessary cells (eg during embryonic development)
  • obsolete cells (eg mammary epithelium at end of lactation)
  • exploitation (chemotherapeutic killing of cells)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is necrosis?

A

unregulated cell death associated with trauma, cellular disruption and an inflammatory response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is apoptosis?

A

programmed cell death NOT associated with inflammatory response
- controlled disassembly of cellular contents without disruption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what happens during necrosis?

A

plasma membrane becomes more permeable -> cell swelling -> rupturing of cellular membranes -> release of proteases -> autodigestion & dissolution of cell -> localised inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what happens during apoptosis?

A

latent phase: death pathways activated but cells appear morphologically the same
execution phase: loss of microvilli & intercellular junctions
- cell shrinkage
- loss of plasma membrane asymmetry (phosphatidylserine appears in outer leaflet)
- chromatin + nuclear condensation
- dna fragmentation
- formation of membrane blebs
- fragmentation into membrane-enclosed apoptotic bodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how can DNA modification during apoptosis be measured?

A

dna in agarose gel separated by size -> dna ‘ladders’ formed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is a tunel assay?

A

fluorescent tags added to ‘ends’ caused by dna fragmentation
- more ends seen in fragmentation -> more fluorescence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are caspases?

A

cysteine-dependent aspartate-directed proteases

  • executioners of apoptosis
  • activated by proteolysis
  • cascade of activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are the 2 subclasses of caspases?

A 
initiator caspases (2,8,9&10)   
effector caspases (3,6&7)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

initiator caspases:

A

have CARD end terminal (caspase recruitment domain)

  • have p20 & p10 domains
  • 8&10 also have DED (death effector domain) before p20&10 effector caspases
  • homotypic (dimerise with same type of caspase eg 8+8)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is caspase maturation?

A

caspases synthesised as procaspases (with prodomain, LS & SS domain) -> prodomains cleaved -> folding of 2 large and 2 small domains to from large hetero-tetramer (activated by heterodimerisation) -> initiates caspase cascades

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

outline the caspase cascades:

A

8 & 9 -> (7) + 3 -> (2 & 1) + 6 -> 10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what do effector caspases do?

A
  • execute apoptotic programme
  • cleave and inactivate proteins / complexes (eg nuclear lamins -> nuclear breakdown)
  • activate enzymes (incl protein kinases, nucleases) by direct cleavage or cleavage of inhibitory molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the mechanisms of caspase activation?

A

death by design (receptor mediated pathways - extrinsic)

death by default (mitochondrial death pathway - intrinsic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are death receptors?

A

trimeric transmembrane ligands

  • all have death domain (DD)
  • signal by connecting with adaptor proteins which recruit other proteins on site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the adapter proteins?

A

proteins needed to trigger intracellular effects (in addition to the ligand + death receptor)

  • FADD (DED + DD) & FLIP (DED)
  • FADD activates & FLIP deactivates
  • DD & DED bind to similar domains on other proteins
17
Q

what happens during the receptor mediated pathway?

A

Fas binds to Fas-L (on plasma membrane of CTLs)
-> ligand brings together three death receptor monomers to form trimer
-> DD of adapter protein (FADD) binds DD of death receptor (Fas)
-> DED of adaptor protein binds DED on procaspase 8 (in this example)
=> this whole complex is called the DISC (death-inducing signalling complex)

-> three procaspases that have been brought together cross-cleave subunits to form their active hetero-tetramer

18
Q

what is FLIP?

A

procaspase analogue
- only has 2 DED domains and no proteolytic activity -> competes with procaspase 8 for DISC binding sites -> reduces caspase activation

19
Q

what happens during the mitochondrial pathway?

A

cellular stress causes damage to mitochondrial membrane

  • > loss of mitochondrial membrane potential (ΔΨ)
  • > membrane becomes leaky
  • > cytochrome C released into cytoplasm
  • > stimulates formation of apoptosome complex
  • > > > caspase released from complex
20
Q

what is the apoptosome?

A

heptamer made up of 7 Apaf-1 profeins (with CARD & WD40 domain)

21
Q

what happens when cytochrome C binds to the apoptosome?

A

7 apaf1 molecules assemble into wheel-like heptamer around their CARD domains

  • > CARD domains on 7 procaspase 9 molecules bind to apoptosome
  • > proximity of procaspases allows cross-cleavage & activation to caspase 9 (similar to in DISC of receptor-mediated pathway)
22
Q

how do energy levels in the cell determine apoptosis v necrosis?

A

apoptosome requires lots of ATP

- so cells with lots of atp will favour apoptosis

23
Q

what proteins modulate apoptosis?

A

Bcl-2

- all contain BH3 domain

24
Q

what are the 2 types of Bcl-2 proteins?

A

anti-apoptotic: associated with mitochrondrial membrane (eg Bcl-2 itself)
pro-apoptotic: in cytosol initially then move to mitochondria (eg Bid)

25
Q

what is Bid?

A

Bcl-2 -> vleaved by caspase 8 of extrinsic pathway -> inserts into the mitochondrial membrane to disrupt ΔΨ -» activates intrinsic pathway too

26
Q

what is Bad?

A

pro-apoptotic Bcl-2 that usually isn’t free to act

27
Q

how is Bad phosphorylated?

A

growth factor binds to RPTK at cell membrane

  • > PI3K (lipid kinase with adapter protein) binds to phosphorylated tyrosin on RPTK
  • > PI3K phosphorylates PIP2 to PIP3
  • > PIP3 acts as docking site for PKB / Akt
  • > PKB/Akt phosphorylates Bad
  • > complexes with 14-3-3 (a protein that just holds Bad -> on mitochondrial membrane Bcl-2 is bound to Bax (via their BH3 domains) however if growth factor is absent Bad is not phosphorylated
  • > displaces Bax from Bcl-2
  • > Bax molecules associate with each other
  • > form pore in mitochondrial membrane
  • > leakiness
  • > apoptosis
28
Q

what is PKB/Akt?

A

proto-oncogene

  • inactivates Bad
  • inactivates caspase 9
  • inactivates pro-apoptotic FOXO transcription factors
  • stimulates protein synthesis
29
Q

what is PTEN?

A

phosphatase that hydrolyses PIP3 -> PIP2 -> therefore PTEN affects how well PKB/Akt pathway inactivates Bad

30
Q

what are IAPs?

A

inhibitors of apoptosis proteins

- bind to procaspases & caspases and inhibit them -> prevents apoptosis

cancer (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions